LncRNA FAM95B1调控胰岛素样生长因子2的表达对宫腔粘连发生的影响

doi:10.3969/j.issn.1006-7795.2023.05.017

首都医科大学学报 ›› 2023, Vol. 44 ›› Issue (5): 821-827.doi: 10.3969/j.issn.1006-7795.2023.05.017

LncRNA FAM95B1调控胰岛素样生长因子2的表达对宫腔粘连发生的影响

巫剑红,田玉翠,蒋子雯,唐世倩,刘朝晖,代荫梅^*

首都医科大学附属北京妇产医院/北京妇幼保健院妇科，北京 100026

收稿日期:2023-01-11 出版日期:2023-10-20 发布日期:2023-10-25
通讯作者: 代荫梅 E-mail:fcyydym@ccmu.edu.cn
基金资助:
北京市卫生健康委员会北京市研究型病房示范建设项目（BCRW202109），首都医科大学附属北京妇产医院北京妇幼保健院“优青人才”计划专项经费资助项目（YQRC201804）

The effect of lncRNA FAM95B1 on the pathogenesis of intrauterine adhesion by regulating insulin-like growth factor 2

Wu Jianhong, Tian Yucui, Jiang Ziwen, Tang Shiqian, Liu Zhaohui, Dai Yinme^i*

Department of Gynecology,Beijing Obstetrics and Gynecology Hospital, Capital Medical University; Beijing Maternal and Child Health Care Hospital, Beijing 100026, China

Received:2023-01-11 Online:2023-10-20 Published:2023-10-25
Supported by:
This study was supported by Beijing Municipal Health Commission, Demonstration Construction Project of Clinical Research Ward (BCRW202109), Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital ‘Excellent Youth’ Plan Special Funds（YQRC201804）.

摘要/Abstract

摘要： 目的探究lncRNA FAM95B1及蛋白编码基因胰岛素样生长因子2（insulin-like growth factor 2，IGF2）对宫腔粘连发生的作用，为宫腔粘连的防治提供新的分子靶点。方法在宫腔粘连组织中采用反转录实时定量聚合酶链反应（reverse transcription-quantitative polymerase chain reaction，RT-qPCR）方法检测lncRNA FAM95B1的mRNA表达水平，采用Western blotting方法检测IGF2及纤维化标志物α-平滑肌肌动蛋白（α-smooth muscle actin，α-SMA）、I型胶原蛋白（collagen type I alpha 1 chain protein，COL1A1）的蛋白表达水平。在经过转化生长因子-β1(transforming growth factor-β1，TGF-β1）处理的子宫内膜基质细胞（endometrial stromal cells，ESCs）中，采用RT-qPCR方法检测lncRNA FAM95B1、IGF2、纤维化标志物（α-SMA、COL1A1、Snail）及上皮标志蛋白E-cadherin的mRNA表达水平。在ESCs中，分别下调lncRNA FAM95B1和IGF2基因，验证二者的调控关系；免疫共沉淀实验检测lncRNA FAM95B1与IGF2的结合关系。然后，si-FAM95B1转染入ESCs中并经过TGF-β1处理，进一步探究lncRNA FAM95B1及IGF2在ESCs向成纤维细胞分化的上皮-间质转化（epithelial-to-mesenchymal transition，EMT）过程中的作用。结果宫腔粘连组织中lncRNA FAM95B1、IGF2及纤维化标志物α-SMA、COL1A1的表达水平上调；经过TGF-β1处理的ESCs中lncRNA FAM95B1、IGF2、纤维化标志物（α-SMA、COL1A1、Snail）的表达水平上调，上皮标志蛋白E-cadherin的表达水平下调。IGF2随lncRNA FAM95B1的变化而变化，而下调IGF2后，lncRNA FAM95B1的表达无明显变化，lncRNA FAM95B1正向调节IGF2；lncRNA FAM95B1与IGF2在TGF-β1处理的ESCs中结合。si-FAM95B1在ESCs向成纤维细胞分化的EMT过程中抑制IGF2的表达，发挥抗纤维化作用。结论 si-FAM95B1可通过下调IGF2的表达抑制宫腔粘连的发生，lncRNA FAM95B1/IGF2轴可能为宫腔粘连的靶向治疗提供新的分子靶点。

关键词: 宫腔粘连, lncRNA FAM95B1, 胰岛素样生长因子2, 上皮-间质转化

Abstract: Objective To investigate the effect of long non-coding RNA (lncRNA) family with sequence similarity 95 member B1(FAM95B1) and insulin-like growth factor 2 (IGF2) on the pathogenesis of intrauterine adhesion. Methods Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to determine the mRNA expression levels of lncRNA FAM95B1, Western blotting was used to determine the protein expression levels of IGF2, α-smooth muscle actin (α-SMA) and collagen type I alpha 1 chain protein (COL1A1) in samples of intrauterine adhesion (IUA) tissue. RT-qPCR was used to determine the mRNA expression levels of lncRNA FAM95B1, IGF2, fibrotic markers (α-SMA, COL1A1, Snail ) and epithelial marker E-cadherin in endometrial stromal cells (ESCs) that had been treated with transforming growth factor-β1 (TGF-β1). Then, lncRNA FAM95B1 and IGF2 genes were down-regulated respectively to verify the regulatory relationship between lncRNA FAM95B1 and IGF2; Co-immunoprecipitation assay was performed to measure the binding relationship between lncRNA FAM95B1 and IGF2. Next, ESCs were transfected with si-FAM95B1 and then were treated with TGF-β1 to investigate the effect of lncRNA FAM95B1 and IGF2 on the transdifferentiation of ESCs into myofibroblasts. Results The expression levels of lncRNA FAM95B1, IGF2, α-SMA and COL1A1 was upregulated in IUA tissues. The mRNA expression levels of lncRNA FAM95B1, IGF2, α-SMA, COL1A1 and Snail were upregulated and the mRNA level of E-cadherin was downregulated in ESCs that had been treated with TGF-β1. IGF2 was positively regulated by lncRNA FAM95B1. LncRNA FAM95B1 and IGF2 were directly bound in TGF-β1-treated ESCs. During the epithelial-to-mesenchymal transition（EMT） of ESCs transdifferentiating into myofibroblasts, si-FAM95B1 exerted antifibrotic effect by down-regulating IGF2. Conclusions si-FAM95B1 inhibits the pathogenesis of IUA by down-regulating IGF2. LncRNA FAM95B1/IGF2 axis may provide novel molecular target for the prevention and treatment of IUA.

Key words: intrauterine adhesions, LncRNA FAM95B1, insulin-like growth factor 2, epithelial-to-mesenchymal transition

中图分类号:

R711.74

巫剑红, 田玉翠, 蒋子雯, 唐世倩, 刘朝晖, 代荫梅. LncRNA FAM95B1调控胰岛素样生长因子2的表达对宫腔粘连发生的影响[J]. 首都医科大学学报, 2023, 44(5): 821-827.

Wu Jianhong, Tian Yucui, Jiang Ziwen, Tang Shiqian, Liu Zhaohui, Dai Yinmei. The effect of lncRNA FAM95B1 on the pathogenesis of intrauterine adhesion by regulating insulin-like growth factor 2[J]. Journal of Capital Medical University, 2023, 44(5): 821-827.

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LncRNA FAM95B1调控胰岛素样生长因子2的表达对宫腔粘连发生的影响

The effect of lncRNA FAM95B1 on the pathogenesis of intrauterine adhesion by regulating insulin-like growth factor 2

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